Mr. A, age 45, reports irritability, loss of interest, sleep disturbance, increased self-criticism, and decreased self care during the last month after a promotion at work. He has a history of 3 major depressive episodes, 1 of which required hospitalization. For the last 2 years his depressive symptoms had been successfully managed with escitalopram, 10 mg/d, plus bupropion, 150 mg/d. Mr. A wants to discontinue these medications because of sexual dysfunction. He asks if nonpharmacologic strategies might help.

One option to consider for Mr. A is mindfulness-based cognitive therapy (MBCT), which was originally developed to help prevent depressive relapse. MBCT also can reduce depression and anxiety symptoms. More recently, MBCT was shown to help individuals discontinue antidepressants after recovering from depression.

Regular mindfulness meditation has been shown to result in structural brain changes that may help explain how the practice effectively addresses psychiatric symptoms (Box). With appropriate training, psychiatrists can help patients reap the benefits of this cognitive treatment.

Regular mindfulness practice has been shown to increase cortical thickness in areas associated with attention, interoception, and sensory processing, such as the prefrontal cortex and right anterior insula.a This supports the hypothesis that mindfulness is a way of attuning the mind to one’s internal processes, and that this involves the same social neural circuits involved in interpersonal attunement—middle prefrontal regions, insula, superior temporal cortex, and the mirror neuron system.b

Amygdala responses. Mindfulness improves affect regulation by optimizing prefrontal cortex regulation of the amygdala. Recent developments in understanding the pathophysiology of depression have highlighted the lack of engagement of left lateral-ventromedial prefrontal circuitry important for the down-regulation of amygdala responses to negative stimuli.c Dispositional mindfulness is associated with greater prefrontal cortical activation and associated greater reduction in amygdala activity during affect labeling tasks, which results in enhanced affect regulation in individuals with higher levels of mindfulness.d

Meditation refers to a variety of practices that intentionally focus attention to help the practitioner disengage from unconscious absorption in thoughts and feelings. Unlike concentrative meditation—in which practitioners focus attention on a single object such as a word (mantra), body part, or external object—in mindfulness meditation participants bring their attention to a wide range of objects (such as breath, body, emotions, or thoughts) as they appear in moment-by-moment awareness.

Clinical Point

Mindfulness is nonjudgmental; each thought, feeling, or sensation is acknowledged and accepted as is

Mindfulness is a nonjudgmental, present-centered awareness in which each thought, feeling, or sensation that arises in the attentional field is acknowledged and accepted as it is.1-3 Bishop et al4 defined a 2-component model of mindfulness:

informal practices, including mindfulness of daily activities such as eating.1

MBSR typically involves 8 to 10 weekly group sessions of 2 to 2.5 hours with 10 to 40 participants with heterogeneous or homogenous clinical presentations. At each session, patients are taught mindfulness skills and practices. Typically, a full day of meditation practice on a weekend follows session 5 or 6. Participants also engage in a daily meditation practice and homework exercises directed at integrating awareness skills into daily life.

Meta-analytic and narrative reviews generally support MBSR’s efficacy for a wide range of clinical presentations, including improved quality of life for chronic pain and cancer patients.5,8-11 Variability in the methodologic rigor of clinical trials of mindfulness-based interventions—such as lack of active control groups and small sample sizes—limits the strength of these studies’ conclusions, however.8

Evidence supporting MBCT comes from randomized, controlled trials (RCTs) and uncontrolled trials (Table 2).12-18 A systematic review of RCTs supported using MBCT in addition to usual care to prevent depressive relapse in individuals with a history of ≥3 depressive episodes.19 Since that review was published, a large RCT (123 patients) comparing antidepressant medication alone to antidepressants plus adjunctive MBCT with support to taper/discontinue antidepressant therapy found:

In this study, MBCT was more effective than maintenance pharmacotherapy in reducing residual depressive symptoms and in improving quality of life; 75% in the MBCT group discontinued antidepressants. MBCT is included in the United Kingdom’s National Institute for Clinical Excellence Clinical Practice Guidelines for Depression20 for prevention of recurrent depression.

Clinical Point

MBCT was shown to reduce depressive symptoms, anxiety, and risk of depressive relapse

Mindfulness for other psychiatric conditions. A review by Toneatto and Nguyen21 of MBSR in the treatment of anxiety and depression symptoms in a range of clinical populations concluded that the evidence supporting a beneficial effect was equivocal. On the other hand, several uncontrolled studies and 1 RCT indicate that mindfulness-based treatments can reduce symptoms in other psychiatric conditions, including eating disorders,22 generalized anxiety disorder,23 bipolar disorder,24 and attention-deficit/hyperactivity disorder.25 Many of these studies were developed to target mood and anxiety symptoms by linking mindfulness and symptom management; this differs from MBSR, which focuses on stress reduction. Methodologically rigorous studies are necessary to evaluate mindfulness-based treatments in these and other psychiatric conditions.

123 patients with recurrent depression treated with antidepressants received maintenance antidepressants alone or adjunctive MBCT with support to taper/discontinue antidepressant therapy

Adjunctive MBCT was as effective as maintenance antidepressants in reducing relapse/recurrence rates but more effective in reducing residual depressive symptoms and improving quality of life; 75% in the MBCT group discontinued antidepressants

You inform Mr. A that MBCT has been shown to improve acute mild-to-moderate depressive symptoms, may decrease his risk of depressive relapse by 50%26 and could help him discontinue his medications.12 He asks how mindfulness exercises will help his symptoms.

How mindfulness works

The assumption that increased mindfulness mediates treatment outcomes4 has been addressed systematically only recently, following the development of operational definitions of mindfulness and self-report mindfulness measures, including the:

Uncontrolled studies using these measures demonstrated that self-reported mindfulness increased following MBSR28,29 and MBCT15,18 in individuals with general stress, anxiety disorder or primary depression, cancer, chronic pain disorder, diabetes, and multiple sclerosis. Accumulating evidence from 1 RCT30 and 2 other uncontrolled studies28,31 demonstrates that mindfulness is associated with symptom reduction following MBSR.

An early refill request for psychostimulants for your college-age patient

﻿Mr. R, age 18, who has been taking amphetamine/dextroamphetamine, 10 mg/d, twice a day, for attention-deficit/hyperactivity disorder since he was age 10, comes to see you shortly after beginning college asking to refill earlier than usual. He says his symptoms are worse since beginning college and he is finding it difficult to focus in class and keep up with the heavy course work. He says he has been taking an extra 10 mg when he “needs the extra boost.” He asks for an early refill and increased dosage. How do you proceed?

Switch to an extended release formulation and increase the dosage to 30 mg/d

Switch to lisdexamfetamine, 30 mg/d

Prescribe amphetamine/dextroamphetamine, 10 mg, on an as-needed basis

Tell Mr. R to take his current prescription as prescribed and discuss the dangers of stimulant abuse. Reassess his symptoms at the next visit.